Disturbances of Kynurenine Pathway of Trytophan Metabolism in Schizophrenia: A Quantitative RT-PCR Study

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Boston,
Massachusetts02114

Purpose:

In this pilot study, the investigators propose to characterize the pattern of activation of
the kynurenine pathway of tryptophan metabolism in peripheral macrophages of patients with
schizophrenia. To do this, the investigators will measure the gene expression of several
major enzymes in this pathway in macrophages, including the key enzyme involved in
tryptophan to kynurenine metabolism, IDO, by means of quantitative reverse-transcription
polymerase chain reaction (RT-PCR). The focus on enzyme mRNA expression as opposed to serum
or cerebrospinal fluid levels of metabolites provides a possibly more sensitive
characterization of the activation of this metabolic pathway.

Study summary:

In this pilot study, we propose to characterize the pattern of activation of the kynurenine
pathway of tryptophan metabolism in peripheral macrophages of patients with schizophrenia.
To do this, we will measure the gene expression of several major enzymes in this pathway in
macrophages, including the key enzyme involved in tryptophan to kynurenine metabolism, IDO,
by means of quantitative reverse-transcription polymerase chain reaction (RT-PCR). The
focus on enzyme mRNA expression as opposed to serum or cerebrospinal fluid levels of
metabolites provides a possibly more sensitive characterization of the activation of this
metabolic pathway.
Primary hypotheses: We hypothesize that patients with schizophrenia will differ in their
expression of macrophage IDO mRNA, reflecting activation of this pathway compared to
normals. We further hypothesize that patients with deficit syndrome will have higher
degrees of enzyme activation.
Secondary hypotheses: Serum tryptophan levels will be lower in patients with schizophrenia
compared to controls, and they will correlate with measures of dysphoria. Serum kynurenine
levels will be elevated in patients with schizophrenia, particularly in deficit syndrome
patients. mRNA expression levels of enzymes downstream from IDO will differ between
patients and controls. Measures of immune activation will be influenced by medical disease
burden (medical comorbidities).